Triglyceride (TG)- rich lipoproteins appear to promote atherogenesis, however, the mechanisms remain largely unknown. The major focus of this proposal is to investigate the interactions of TG-rich lipoproteins with perfused blood vessels. The investigator hypothesizes that: [1] Lipoprotein lipase (LpL) serves as a molecular bridge between glycosaminoglycans of the artery wall and TG-rich lipoproteins. This effect increases binding of lipoproteins to the wall and decreases efflux. [2] Hydrolysis of TG- rich lipoproteins by LpL results in lipolysis products that injure endothelium. Injury to endothelium increases lipoprotein permeability into the vascular wall. The investigations are performed in recently developed perfused artery (hamster aorta) and microvessel (hamster mesentery) models. The rate of fluorescently labeled TG-rich lipoprotein accumulation and efflux from the vascular wall are determined by quantitative fluorescence microscopy. The specific aims are: [1] To investigate mechanisms causing increased TG-rich lipoprotein binding in arteries perfused with TG-rich lipoproteins and LpL. The arteries will be treated with heparin (which prevents LpL binding to glycosaminoglycans), antibodies to the amino-terminal region of apolipoprotein B (which facilitates binding of LpL to cells) and antibodies to LpL (which prevents the interaction of TG-rich lipoproteins with LpL). [2] To examine transendothelial flux of lipoproteins during lypolysis of TG-rich lipoproteins. For this aim macromolecule flux will be measured during perfusion of unlabeled TG-rich lipoproteins and LpL or lipolysis products only. Using the described experimental preparation to measure lipoprotein flux and image accumulation in the artery wall can be measured simultaneously while perfusate and superfusate composition, flow and hydrostatic pressure are controlled. These advantages enable the investigator to measure artery lipoprotein flux directly and in real time to study lipoprotein-vascular wall interactions in individually perfused arteries. This experimental undertaking will provide new information on TG-rich lipoprotein-artery wall interactions and possible mechanisms of atherogenesis.